A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration

ABSTRACT In the production of biopharmaceuticals disk‐stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot‐scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale‐down approach based upon the use of a shear device and a bench‐top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large‐scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited. Biotechnol. Bioeng. 2016;113: 1934–1941. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. This study describes the development of a scale‐down approach in order to mimic the performance of a pilot‐scale centrifuge for cell culture clarification. This approach was also utilized as a preparative methodology to produce representative centrate to test subsequent polishing filter capacity. The proposed method enables users to characterize effects of cell culture conditions and large‐scale centrifuge parameters on the performance of the harvest sequence at an early stage of process development when material is limited for such studies.